This project starts with a large computer model of the part of cardiac metabolism (glycolysis, the Krebs cycle, the membrane transport mechanisms which move their intermediates, and some related metabolism) which represents the principal energy providing the consuming pathways in the heart, and which now represents 68 enzymes. There is also a body of techniques and software which has been used to build it. This model contains crude approximations of certain important pathways or areas of metabolism, which will be replaced by accurate and rigorous submodels: fatty acid oxidation, glycogen metabolism, several aspects of adenine nucleotide metabolism, lactate permease. Ca ions metabolism will be added to the model, largely by incorporation of these accurate submodels. The resulting model will be used to stimulate several important normal-flow perfused rat heart preparations, particularly to investigate extreme cardiac work conditions or perfusion with substrates that provide a good test of the model. We will then construct a variant of this model which accounts for the effects of ischemia, and stimulate some ischemic preparation. Most of the effort in simulating ischemia will be devoted to investigating the complicating effects of diabetes in ischemic hearts and the metabolic consequences of therapies involving insulin. Improvements will be made in the techniques of building and interpreting these models, particularly formalization of presently-used intuitive techniques, and application of sensitivity analysis and better graphical techniques. The software presently used with the model will be improved for more efficient solution of our mixture of stiff differential equations and algebraic equations, for more effective use of time-slice techniques which greatly reduce the required number of solutions of the differential equations, and to perform some additional functions.